One cardinal property of the adaptive immune system is diversity: the immune system must be able to recognize and respond to virtually any invading microorganism. In order to generate such diversity, developing B and T cells rearrange a defined set of variable (V), diversity (D), and joining (J) gene segments, with N-nucleotide addition and subtraction at the joints of these gene segments, resulting in a semi-random CDR3 repertoire of immune receptors. Further diversity is generated by pairing of rearranged alpha and beta (for the T cell receptor (TCR)) or heavy and light chain (for the B cell receptor (BCR)).
Current technologies allow for analysis of CDR3 diversity within either the alpha or beta TCR (or heavy and light chain BCR), but no current methods exist for obtaining both CDR3 from individual cells from large polyclonal populations: single cell sequencing remains too expensive while molecular strategies for obtaining linked CDR3 information from single cells have not been adequately developed.